IVUS-Guided Sirolimus-Coated Balloon Versus Sirolimus-Eluting Stent for De Novo Large Vessel Lesions in ACS

IVUS-Guided Sirolimus-Coated Balloon Versus Sirolimus-Eluting Stent for De Novo Large Vessel Lesions in ACS: A Non-Inferiority Randomized Controlled Trial

The goal of this interventional study is to evaluate the efficacy and safety of an intravascular ultrasound (IVUS)-guided sirolimus-coated balloon (SCB)-based strategy versus planned sirolimus-eluting stent (SES) implantation in patients with acute coronary syndrome (ACS) and de novo large-vessel coronary lesions. The main question is whether the SCB-based strategy is non-inferior to the SES strategy with respect to in-segment late lumen loss (LLL) at 9 months. Following adequate lesion preparation and confirmation according to the prespecified angiographic and IVUS criteria that the target lesion is suitable for both randomized treatment strategies, participants will be randomly assigned to undergo either SCB treatment without routine stent implantation or planned SES implantation. In the SCB group, bail-out SES implantation will be performed when clinically necessary, such as in cases of significant residual stenosis or flow-limiting dissection. Participants will undergo angiographic and IVUS follow-up at 9 months, and clinical outcomes will be assessed through 12 months.

Lesion preparation will be performed before randomization. Individuals with unsuccessful lesion preparation will be considered pre-randomization failures and will not be assigned to either study arm. The reason for unsuccessful lesion preparation, the treatment subsequently received, and limited safety information through 48 hours after the procedure will be documented for screening and safety oversight purposes only. These individuals will not undergo protocol-mandated follow-up and will not be included in the efficacy or comparative safety analyses of the randomized trial.

Inclusion Criteria

All of the following criteria must be met:

1. Aged ≥18 years.
2. Diagnosed with acute coronary syndrome (ACS), including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), or ST-segment elevation myocardial infarction (STEMI). The diagnosis, classification, and clinical management of ACS will follow the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. NSTEMI and STEMI will be diagnosed according to the Fourth Universal Definition of Myocardial Infarction.
3. A de novo lesion in a large native coronary artery with a target lesion reference vessel diameter ≥2.75 mm.
4. Only one target lesion is considered to require intervention and is suitable for treatment with a sirolimus-coated balloon (SCB), with bail-out stenting if necessary, or with a sirolimus-eluting stent (SES).
5. Successful lesion preparation according to the prespecified angiographic and IVUS criteria, confirming that the target lesion is suitable for both randomized treatment strategies.
6. The participant has fully understood the study and provided written informed consent.

Exclusion Criteria

Participants meeting any of the following criteria will be excluded:

1. Acute heart failure, acute cardiogenic shock, or persistent hemodynamic instability.
2. Percutaneous coronary intervention within the previous 12 months, including stent implantation, balloon angioplasty, or SCB treatment.
3. A bifurcation lesion requiring simultaneous intervention of both the main vessel and side branch.
4. In-stent restenosis in the target vessel; only de novo lesions are eligible for this study.
5. Lesion anatomy unsuitable for SCB treatment or conventional SES implantation, including:

i. Lesion length >40 mm.

ii. Chronic total occlusion (CTO).

iii. A left main coronary artery target lesion or severe left main coronary artery disease requiring simultaneous treatment.

iv. Severe calcification expected to preclude satisfactory lesion preparation.

v. Severe vessel tortuosity or angulation >90° that may prevent safe device delivery.

vi. A bypass graft lesion or myocardial bridging involving the target lesion.

f. Severe hepatic or renal impairment.

g. A concomitant condition associated with a life expectancy of less than 1 year.

h. Previous coronary artery bypass grafting (CABG).

i. Unsuitable for percutaneous coronary intervention or long-term antithrombotic therapy, including:

Known contraindication to aspirin, heparin, antiplatelet agents, or contrast media.

A history of intracranial hemorrhage. Pregnancy, breastfeeding, or planned pregnancy during the study period.

j. Previous prosthetic heart valve replacement.

k. Participation in another clinical study or clinical trial within the previous 12 months.

l. Known severe hypersensitivity to sirolimus or its derivatives, any component of the study devices-including the SES polymer or metal-or contrast media; or inability or unwillingness to undergo repeat coronary angiography and IVUS at 9 months for any other reason.

m. Considered unsuitable for enrollment by the investigator because of anticipated nonadherence or any other reason.